This project will examine the relative roles of genetic background, exercise, and aging on bone performance, using two new approaches. First, mice, which are of known genetic background and which have been selected for high levels of voluntary exercise, will be raised with and without access to a running wheel. This will allow genetic and exercise effects on skeletal function to be statistically separated from one another. Second, a comprehensive bone analysis approach will be used, in which the entire proximal femur will be studied, from microscale material properties to gross bone morphology. Nanoindentation and micro-computed tomography will allow highly accurate finite element analysis of the mouse femora. Additional aims of this project include the determination of mineralization and remodeling patterns in response to exercise, the identification of areas of high stress in the femur during locomotion, and evaluation of models of fracture mechanics. In addition to the fundamental questions of bone biology addressed in this project, the results will permit a better understanding of the relationship between genetics, exercise, and aging, which will have significant implications for the prediction and diagnosis of osteoporosis. [unreadable] [unreadable]